Department of Nuclear Medicine, China-Japan Union Hospital, Jilin University, Changchun 130033, China.
Department of Breast Surgery, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan 250012, China.
Contrast Media Mol Imaging. 2017 Jul 11;2017:4972701. doi: 10.1155/2017/4972701. eCollection 2017.
Chemotherapy is a powerful cancer treatment but suffers from poor biocompatibility and a lack of tumor targeting. Here, we developed a CD44-targeted polymeric nanocomplex by encapsulating 10-hydroxycamptothecin (HCPT) into hyaluronic acid nanoparticles (HANP) for targeted cancer therapy. In vitro, the HANP/HCPT showed improved cytotoxicity to five cancer cell lines including HT29, A549, MDA-MB-231, HepG2, and MDA-MB-435 versus free HCPT. After systemic administration into MDA-MB-231 breast cancer xenograft, tumor growth was significantly inhibited 5.25 ± 0.21 times in the HANP/HCPT treated group relative to the nontreated group. In addition, the treatment response was also accessed and confirmed by 18F-fluoro-2-deoxy-D-glucose ([18F] FDG) positron emission tomography (PET). The MDA-MB-231 tumors responded to HANP/HCPT 7 days after the first treatment, which benefits treatment strategy adjustment and personalization. No apparent systemic toxic effects were seen in mice treated with HANP/HCPT. In summary, the HANPs have great promise as a targeted drug carrier for cancer chemotherapy. Our HANP platform can also deliver other hydrophobic chemotherapy agents.
化疗是一种强大的癌症治疗方法，但存在生物相容性差和缺乏肿瘤靶向性的问题。在这里，我们通过将 10-羟基喜树碱（HCPT）包封到透明质酸纳米颗粒（HANP）中，开发了一种 CD44 靶向的聚合物纳米复合物，用于靶向癌症治疗。在体外，HANP/HCPT 对包括 HT29、A549、MDA-MB-231、HepG2 和 MDA-MB-435 在内的五种癌细胞系的细胞毒性均优于游离 HCPT。在 MDA-MB-231 乳腺癌异种移植模型中进行系统给药后，与未治疗组相比，HANP/HCPT 处理组的肿瘤生长显著抑制了 5.25±0.21 倍。此外，还通过 18F-氟-2-脱氧-D-葡萄糖 ([18F]FDG) 正电子发射断层扫描 (PET) 评估和确认了治疗反应。在第一次治疗后 7 天，MDA-MB-231 肿瘤对 HANP/HCPT 有反应，这有利于治疗策略的调整和个性化。用 HANP/HCPT 治疗的小鼠未出现明显的全身毒性作用。总之，HANP 有望成为癌症化疗的靶向药物载体。我们的 HANP 平台还可以递送其他疏水性化疗药物。
